Tailored therapeutic decision of rheumatoid arthritis using proteomic strategies: how to start and when to stop?

Unpredictable treatment responses have been an obstacle for the successful management of rheumatoid arthritis. Although numerous serum proteins have been proposed, there is a lack of integrative survey to compare their relevance in predicting treatment outcomes in rheumatoid arthritis. Also, little is known about their applications in various treatment stages, such as dose modification, drug switching or withdrawal. Here we present an in-depth exploration of the potential usefulness of serum proteins in clinical decision-making and unveil the spectrum of immunopathology underlying responders to different drugs. Patients with robust autoimmunity and inflammation are more responsive to biological treatments and prone to relapse during treatment de-escalation. Moreover, the concentration changes of serum proteins at the beginning of the treatments possibly assist early recognition of treatment responders. With a better understanding of the relationship between the serum proteome and treatment responses, personalized medicine in rheumatoid arthritis will be more achievable in the near future.

Quinazolinone-Peptido-Nitrophenyl-Derivatives as Potential Inhibitors of SARS-CoV-2 Main Protease.

The severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2-Mpro) plays an essential role in viral replication, transcription, maturation, and entry into host cells. Furthermore, its cleavage specificity for viruses, but not humans, makes it a promising drug target for the treatment of coronavirus disease 2019 (COVID-19). In this study, a fragment-based strategy including potential antiviral quinazolinone moiety and glutamine- or glutamate-derived peptidomimetic backbone and positioned nitro functional groups was used to synthesize putative Mpro inhibitors. Two compounds, G1 and G4, exhibited anti-Mpro enzymatic activity in a dose-dependent manner, with the calculated IC50 values of 22.47 ± 8.93 µM and 24.04 ± 0.67 µM, respectively. The bio-layer interferometer measured real-time binding. The dissociation kinetics of G1/Mpro and G4/Mpro also showed similar equilibrium dissociation constants (KD) of 2.60 × 10-5 M and 2.55 × 10-5 M, respectively, but exhibited distinct association/dissociation curves. Molecular docking of the two compounds revealed a similar binding cavity to the well-known Mpro inhibitor GC376, supporting a structure-function relationship. These findings may open a new avenue for developing new scaffolds for Mpro inhibition and advance anti-coronavirus drug research.

Investigation on Musculoskeletal Injury and Psychological Empowerment of Reflexologists in Taiwan: Analysis of the Recognition to Alternative Therapy.

Many studies have proven that reflexology has been used as a complementary medical treatment. Therefore, the government has started to plan an examination system for reflexology personnel to ensure the quality of service. Reflexologists work long hours, have heavy workloads, and perform poses that do not conform to human factors, which often cause musculoskeletal fatigue. The purpose of this study is to understand the musculoskeletal pain conditions of reflexologists, the psychological empowerment status, and the perceptions of complementary medicine therapy. The data for this study were obtained in two ways: (1) 59 practitioners were surveyed by using a face-to-face questionnaire and (2) a semi-structured interview was carried out for 10 practitioners. This study discovered the following: (1) Reflexology practitioners have musculoskeletal discomfort symptoms in body parts, including the left shoulder (25.4%), left hand or wrist (25.4%), lower back (25.4%), right shoulder (23.7%), left elbow or forearm (22%). (2) Reflexology practitioners are highly psychologically empowered to work. (3) The practitioners of foot therapy hold a positive attitude towards foot therapy and believe that foot therapy is a natural therapy, which is self-serving and can help others. (4) Most reflexologists support the government's desire to promote the reflexology examination system and are willing to help develop the policy. (5) The height of most reflexologist work chairs does not match the height of the guest's seat and is not ergonomic.

Nature-Inspired Surface Structures Design for Antimicrobial Applications.

Surface contamination by microorganisms such as viruses and bacteria may simultaneously aggravate the biofouling of surfaces and infection of wounds and promote cross-species transmission and the rapid evolution of microbes in emerging diseases. In addition, natural surface structures with unique anti-biofouling properties may be used as guide templates for the development of functional antimicrobial surfaces. Further, these structure-related antimicrobial surfaces can be categorized into microbicidal and anti-biofouling surfaces. This review introduces the recent advances in the development of microbicidal and anti-biofouling surfaces inspired by natural structures and discusses the related antimicrobial mechanisms, surface topography design, material application, manufacturing techniques, and antimicrobial efficiencies.

In vitro evaluation of injectable Tideglusib-loaded hyaluronic acid hydrogels incorporated with Rg1-loaded chitosan microspheres for vital pulp regeneration.

Injectable systems receive attention in endodontics due to the complicated and irregular anatomical structure of root canals. Here, injectable Tideglusib (Td)-loaded hyaluronic acid hydrogels (HAH) incorporated with Rg1-loaded chitosan microspheres (CSM) were developed for vital pulp regeneration, providing release of Td and Rg1 to trigger odontoblastic differentiation of human dental pulp stem cells (DPSC) by Td and vascularization of pulp by Rg1. The optimal concentrations were determined as 90 nM and 50 µg/mL for Td and Rg1, and loaded in HA and CSM in HAH, respectively. Odontogenic (COL1A1, ALP, OCN, Axin-2, DSPP, and DMP1) and angiogenic (VEGFA, VEGFR2, and eNOS) differentiation of DPSC cultured in the presence of hydrogels was shown at gene expression level. Our results suggest that our injectable hydrogel formulation has potential to improve strategies for vital pulp regeneration. In vivo evaluations are needed to test the feasibility and potential of these hydrogels for vital pulp regeneration.

Foot Reflexology: Recent Research Trends and Prospects.

Foot reflexology is a non-invasive complementary therapy that is increasingly being accepted by modern people in recent years. To understand the research trends and prospects of foot reflexology in the past 31 years, this study used the Web of Science core collection as the data source and two visualization tools, COOC and VOSviewer, to analyze the literature related to the field of foot reflexology from 1991 to 2021. This study found that the number of articles published in the field of foot reflexology has been increasing year by year, and the top three journals with the most articles are Complementary Therapies in Clinical Practice, Therapies in Medicine, and the Journal of Alternative and Complementary Medicine. The top three most prolific authors are Wyatt, Sikorskii, and Victorson, and the core institutions in the field of foot reflexology are Michigan State University, Northwestern University, Tehran University of Medical Sciences, and the University of Exeter. Foot reflexology has been shown to have a moderating effect on anxiety, fatigue, and cancer, and is a topic of ongoing and future research. This study uses this bibliometric analysis of foot reflexology literature to provide an overview of prior knowledge and a reference direction for modern preventive medicine.

The Synthesis of Europium-Doped Calcium Carbonate by an Eco-Method as Free Radical Generator Under Low-Intensity Ultrasonic Irradiation for Body Sculpture.

Body sculpture is a common method to remove excessive fat. The diet and exercise are the first suggestion to keep body shape; however, those are difficult to keep adherence. Ultrasound has been developed for fat ablation; however, it could only serve as the side treatment along with liposuction. In the study, a sonosensitizer of europium-doped calcium carbonate (CaCO3: Eu) would be synthesized by an eco-method and combined with low-intensity ultrasound for lipolysis. The crystal structure of CaCO3: Eu was identified by x-ray diffractometer (XRD). The morphology of CaCO3: Eu was analyzed by scanning electron microscope (SEM). The chemical composition of CaCO3: Eu was evaluated by energy-dispersed spectrophotometer (EDS) and inductively coupled plasma mass spectrometer (ICP-MS). The electronic diffraction pattern was to further check crystal structure of the synthesized individual grain by transmission electron microscope (TEM). The particle size was determined by Zeta-sizer. Water-soluble tetrazolium salt (WST-1) were used to evaluate the cell viability. Chloromethyl-2',7'-dichlorofluorescein diacetate (CM-H2DCFDA) and live/dead stain were used to evaluate feasibility in vitro. SD-rat was used to evaluate the safety and efficacy in vivo. The results showed that CaCO3: Eu had good biocompatibility and could produce reactive oxygen species (ROS) after treated with low-intensity ultrasound. After 4-weeks, the CaCO3: Eu exposed to ultrasound irradiation on SD rats could significantly decrease body weight, waistline, and subcutaneous adipose tissue. We believe that ROS from sonoluminescence, CO2-bomb and locally increasing Ca2+ level would be three major mechanisms to remove away adipo-tissue and inhibit adipogenesis. We could say that the combination of the CaCO3: Eu and low-intensity ultrasound would be a non-invasive treatment for the body sculpture.

CCL2 associated with CD38 expression during ex vivo expansion in human cord blood-derived hematopoietic stem cells.

To date, different experimental strategies have been developed for the ex vivo expansion of human hematopoietic stem cells (HSCs) for clinical applications. However, differences in the genomic function of expanded HSCs under different culture systems remain unclear. In this study, we compared the gene expression profiles of HSCs in ex vivo expanded serum (10% FBS, fetal bovine serum) and serum-free culture systems and analyzed the molecular functions of differentially expressed genes using microarray chips. We identified 839 differentially expressed genes between the two culture systems. These genes were enriched in the TNF -regulated inflammatory pathway in an FBS culture system. In addition, the mRNA expression of CCL2 (C-C motif chemokine ligand 2), TNF (tumor necrosis factor) and FOS (FBJ murine osteosarcoma viral oncogene homolog) was validated by RT-qPCR. Our data revealed that ex vivo expansion of HSCs using the FBS culture system induces an inflammatory response and high CD38 expression, indicating that this system might activate an inflammatory pathway and induce expression of the cancer marker CD38 during ex vivo expansion of HSCs. This study provides a transcriptional profile and new insights into the genomic functions of HSCs under different expanded cultures.

The Synthesis and Evaluation of RGD-Conjugated Chitosan Gel as Daily Supplement for Body Weight Control.

(1) Background: Obesity is one of the most widespread chronic diseases and increases the risk of several other chronic diseases, especially type 2 diabetes. (2) Methods: Endobarrier is a new medical device what is worn in the small intestines for the treatment of type 2 diabetes and obesity. However, given the invasive and other adverse effects of the Endobarrier, we propose the use of RGD peptide conjugated with chitosan (RC) as an alternative. (3) Results: The FTIR and NMR spectrum showed RGD peptide was successfully conjugated on chitosan and RGD-CT is retained in the small intestine even after digestion. In vitro of wst-1 and live and dead staining studies show that the RGD-CT gel is highly biocompatible and non-toxic. Rats treated with the RGD-CT gel for a short term showed significant decrease change more than 30% in body weight, while the blood and hematic biometrics were within normal values. (4) Conclusions: The RGD-CT gel is safe, suitable for the short-term, reducing visceral fat rate health food to control weight. In the future, it is expected to develop a safe, long-term effective, flexibility of use and low-side-effect anti-obesity therapy in the era of precision medicine by further modification.

Kartogenin Enhances Chondrogenic Differentiation of MSCs in 3D Tri-Copolymer Scaffolds and the Self-Designed Bioreactor System.

Human cartilage has relatively slow metabolism compared to other normal tissues. Cartilage damage is of great clinical consequence since cartilage has limited intrinsic healing potential. Cartilage tissue engineering is a rapidly emerging field that holds great promise for tissue function repair and artificial/engineered tissue substitutes. However, current clinical therapies for cartilage repair are less than satisfactory and rarely recover full function or return the diseased tissue to its native healthy state. Kartogenin (KGN), a small molecule, can promote chondrocyte differentiation both in vitro and in vivo. The purpose of this research is to optimize the chondrogenic process in mesenchymal stem cell (MSC)-based chondrogenic constructs with KGN for potential use in cartilage tissue engineering. In this study, we demonstrate that KGN treatment can promote MSC condensation and cell cluster formation within a tri-copolymer scaffold. Expression of Acan, Sox9, and Col2a1 was significantly up-regulated in three-dimensional (3D) culture conditions. The lacuna-like structure showed active deposition of type II collagen and aggrecan deposition. We expect these results will open new avenues for the use of small molecules in chondrogenic differentiation protocols in combination with scaffolds, which may yield better strategies for cartilage tissue engineering.

Using C-doped TiO2 Nanoparticles as a Novel Sonosensitizer for Cancer Treatment.

Sonodynamic therapy is an effective treatment for eliminating tumor cells by irradiating sonosentitizer in a patient's body with higher penetration ultrasound and inducing the free radicals. Titanium dioxide has attracted the most attention due to its properties among many nanosensitizers. Hence, in this study, carbon doped titanium dioxide, one of inorganic materials, is applied to avoid the foregoing, and furthermore, carbon doped titanium dioxide is used to generate ROS under ultrasound irradiation to eliminate tumor cells. Spherical carbon doped titanium dioxide nanoparticles are synthesized by the sol-gel process. The forming of C-Ti-O bond may also induce defects in lattice which would be beneficial for the phenomenon of sonoluminescence to improve the effectiveness of sonodynamic therapy. By dint of DCFDA, WST-1, LDH and the Live/Dead test, carbon doped titanium dioxide nanoparticles are shown to be a biocompatible material which may induce ROS radicals to suppress the proliferation of 4T1 breast cancer cells under ultrasound treatment. From in vivo study, carbon doped titanium dioxide nanoparticles activated by ultrasound may inhibit the growth of the 4T1 tumor, and it showed a significant difference between sonodynamic therapy (SDT) and the other groups on the seventh day of the treatment.

Enhancement of Neurite Outgrowth by Warming Biomaterial Ultrasound Treatment.

Ultrasound is a method for enhancing neurite outgrowth because of its thermal effect. In order to reach the working temperature to enhance neurite outgrowth, long-time treatment by ultrasound is necessary, while acknowledging that the treatment poses a high risk of damaging nerve cells. To overcome this problem, we developed a method that shortens the ultrasonic treatment time with a warming biomaterial. In this study, we used Fe3O4 nanoparticle-embedded polycaprolactone (PCL) as a sonosensitized biomaterial, which has an excellent heating rate due to its high acoustic attenuation. With this material, the ultrasonic treatment time for enhancing neurite outgrowth could be effectively shortened. Ultrasonic treatment could also increase neuronal function combined with the warming biomaterial, with more promoter neuronal function than only ultrasound. Moreover, the risk of overexposure can be avoided by the use of the warming biomaterial by reducing the ultrasonic treatment time, providing better effectiveness.

Cooperative impact of thiazolidinedione and fatty acid synthase on human osteogenesis.

Previous, we found that the small molecules capable of inhibiting the expression and the pro-adipogenic activity of ZNF521 might improve the osteogenic performance of aging human bone marrow MSCs (bmMSCs), and that fatty acid synthase (FASN) was a critical effector of ZNF521's pro-adipogenic activity. Here, by characterizing the netoglitazone (MCC-555), one of the thiazolidinediones known as adipogenic enhancers, as an inhibitor of ZNF521 expression, we found that MCC-555 indeed also harbored pro-osteoblastic effect. Investigation revealed that MCC-555 might function as a GSK3ß inhibitor to promote osteoblastogenesis and bone formation. Importantly, combination of MCC-555 with FASN knockdown, but not with GW9662 (a PPARγ2 antagonist), blocked the pro-adipogenic but retained the pro-osteoblastic effect of MCC-555. Using a 3-dimentional culture system, we showed that MCC-555 facilitated the FASN-knockdown of aging human bmMSCs to form cell clusters in scaffolds, and to promote osteoblastic differentiation and biomineralization in cell clusters. These data indicated that MCC-555 promoted bmMSCs to produce bone-like tissues. Our data narrate a thiazolidinedione-based novel strategy to improve the osteogenic performance of aging bmMSCs to support the application of autologous aging bmMSCs in cell therapy and in producing bone-like tissues for repairing bone injury in the elderly.

Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells.

Many studies have indicated that loss of the osteoblastogenic potential in bone marrow mesenchymal stem cells (bmMSCs) is the major component in the etiology of the aging-related bone deficit. But how the bmMSCs lose osteogenic capability in aging is unclear. Using 2-dimentional cultures, we examined the dose response of human bmMSCs, isolated from adult and aged donors, to exogenous insulin-like growth factor 1 (IGF-1), a growth factor regulating bone formation. The data showed that the mitogenic activity and the osteoblastogenic potential of bmMSCs in response to IGF-1 were impaired with aging, whereas higher doses of IGF-1 increased the proliferation rate and osteogenic potential of aging bmMSCs. Subsequently, we seeded IGF-1-overexpressing aging bmMSCs into calcium-alginate scaffolds and incubated in a bioreactor with constant perfusion for varying time periods to examine the effect of IGF-1 overexpression to the bone-forming capability of aging bmMSCs. We found that IGF-1 overexpression in aging bmMSCs facilitated the formation of cell clusters in scaffolds, increased the cell survival inside the cell clusters, induced the expression of osteoblast markers, and enhanced the biomineralization of cell clusters. These results indicated that IGF-1 overexpression enhanced cells' osteogenic capability. Thus, our data suggest that the aging-related loss of osteogenic potential in bmMSCs can be attributed in part to the impairment in bmMSCs' IGF-1 signaling, and support possible application of IGF-1-overexpressing autologous bmMSCs in repairing bone defect of the elderly and in producing bone graft materials for repairing large scale bone injury in the elderly.

Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells.

Gelatin is an efficient drug delivery vehicle for attaching targeting molecules like phytohemagglutinin erythroagglutinating (PHA-E) and carrying the chemotherapeutic agent gemcitabine (GEM). Fluorescent gelatin nanoparticles (GNPs) conjugated with PHA-E and carrying gemcitabine (GNP-(PHA-E)-GEM) were synthesized by nanoprecipitation for guiding gemcitabine-loaded gelatin nanoparticles to NSCLC by PHA-E targeting. GNPs have a uniform narrow size distribution and spherical shape, and their particle size is about 290 nm. The release rate of gemcitabine from nanoparticles reached the plateau of the curve at approximately 30% within 72 hours. PHA-E conjugated nanoparticles could enhance the cellular accumulation of nanoparticles. The results showed that GNP-(PHA-E)-GEM treatment caused an increase of cell growth inhibition and cytotoxicity on NSCLC cells A-549 and H292. In an Annexin V/PI assay, treatment with GNP-(PHA-E)-GEM could induce apoptosis of cancer cells. Treatment of NSCLC cells with GNP-(PHA-E)-GEM firstly resulted in time-dependent inhibition of epidermal growth factor receptor (EGFR) and Akt phosphorylation. And it also could increase p53 phosphorylation. And then it could decrease Bad phosphorylation and increase Bax. Finally, it could result in enhancing the release of cytochrome c, which thus increases caspase-9 and caspase-3. In conclusion, GNP-(PHA-E)-GEM could induce growth inhibition and cytotoxicity, which was mediated through inhibition of EGFR phosphorylation and the switching on of p53 that causes cell apoptosis of NSCLC cells A-549 and H292. It's significant to conjugate PHA-E for targeting cancer and inhibiting EGFR phosphorylation as it could decrease the dosage of gemcitabine, which reduces side effects on normal tissue. GNP-(PHA-E)-GEM has great potential for NSCLC treatment.

Fabrication of keratin/fibroin membranes by electrospinning for vascular tissue engineering.

Cardiovascular diseases (CVDs) are some of the leading causes of death and bypass surgery is one of the common treatment options for the critical CVD patients. There is no ideal material available for arterial bypass surgery. Herein, a fibroin and keratin porous membrane was prepared by electro-spinning and proposed for tissue-engineered vascular grafts (TEVGs). The purified fibroin (F) and keratin (K) were mixed in different weight ratios of 9 : 1 (FK91), 8 : 2 (FK82), and 7 : 3 (FK73) to obtain a membrane. The SEM images revealed that the electro-spinned membranes have a fibrous interconnected porous structure. The average diameter of the membrane F, FK91, FK82 and FK73 was 5.74 ± 1.04, 4.20 ± 1.19, 2.94 ± 0.81 and 2.27 ± 0.65 µm, respectively. The ultimate tensile strength (UTS) of F, FK91, FK82 and FK73 was 2.09 ± 0.06, 2.02 ± 0.06, 1.81 ± 0.10 and 1.74 ± 0.12 MPa, respectively. The contact angle of F, FK91, FK82 and FK73 was 72.55 ± 0.55°, 66.39 ± 0.90°, 43.47 ± 0.04° and 33.65 ± 2.83°, respectively. The wettability results were in agreement with those of the cell adhesion to the electro-spinning membranes. The attached HUVECs on the developed membranes showed no cytotoxicity. The immunocytochemistry staining and qPCR analysis showed that the phenotype of the keratin-fibroin membrane was not altered. The results of the ultimate tensile strength, cell adhesion and microstructure revealed that FK82 is similar to native vessels and could be considered as a potential material for TEVGs.

3D cell clusters combined with a bioreactor system to enhance the drug metabolism activities of C3A hepatoma cell lines.

Since clinical drugs need to be approved for their liver metabolism efficiency before commercialization, a powerful in vitro drug-screening platform is imperative and indispensable for the clinical medicine and pharmaceutical industries. An essential issue in the development of drug screening platforms is choosing cell candidates that mimic and perform cell/tissue functions of normal hepatic tissues in vivo. In this study, we developed a self-designed bioreactor system to provide and mimic an appropriate environment for systematic cell expansion, micro-tissue formation, and increased cellular cytochrome P450 (CYP) enzymatic activities. Since CYP3A4 is the most plentiful and crucial enzyme in drug metabolism among liver CYP superfamily members, we demonstrated that micro-tissue formation under three-dimensional dynamic conditions could enhance cellular CYP3A4 enzymatic activity, maintain cell viability, and preserve adhesive abilities. Furthermore, Ca-alginate scaffolds used in this study can be completely removed by a non-toxic chelating reagent (EDTA solution), and the functional micro-tissues can be collected by slow-speed centrifugation. In conclusion, these micro-tissues are advantageous and show great potential in in vitro drug metabolizing assays.

Radix Scrophulariae extracts (harpagoside) suppresses hypoxia-induced microglial activation and neurotoxicity.

BACKGROUND: Hypoxia could lead to microglia activation and inflammatory mediators' overproduction. These inflammatory molecules could amplify the neuroinflammatory process and exacerbate neuronal injury. The aim of this study is to find out whether harpagoside could reduce hypoxia-induced microglia activation. METHODS: In this study, primary microglia cells harvested from neonatal ICR mice were activated by exposure to hypoxia (1 % O2 for 3 h). Harpagoside had been shown to be no cytotoxicity on microglia cells by MTT assay. The scavenger effect of harpagoside on hypoxia-enhanced microglial cells proliferation, associated inflammatory genes expression (COX-II, IL-1ß and IL-6 genes) and NO synthesis were also examined. RESULTS: Hypoxia enhances active proliferation of microglial cells, while harpagoside can scavenge this effect. We find that harpagoside could scavenge hypoxia-enhanced inflammatory genes expression (COX-2, IL-1ß and IL-6 genes) and NO synthesis of microglial cells. Under 3 h' hypoxic stimulation, the nuclear contents of p65 and hypoxia inducible factor-1α (HIF-1α) significantly increase, while the cytosol IκB-α content decreases; these effects can be reversed by 1 h's pre-incubation of 10(-8) M harpagoside. Harpagoside could decrease IκB-α protein phosphorylation and inhibit p65 protein translocation from the cytosol to the nucleus, thus suppress NF-κB activation and reduce the HIF-1α generation. CONCLUSION: These results suggested that the anti-inflammatory mechanism of harpagoside might be associated with the NF-κB signaling pathway. Harpagoside protect against hypoxia-induced toxicity on microglial cells through HIF-α pathway.

3D porous calcium-alginate scaffolds cell culture system improved human osteoblast cell clusters for cell therapy.

Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.

Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1ß-induced catabolic gene expression in cartilage.

BACKGROUND: In osteoarthritis (OA), the imbalance of chondrocytes' anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1ß) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1ß-induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA. METHODS: Chondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2α (EPAS1) in cartilage catabolism simulated by IL-1ß (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1ß-induced inflammatory conditions and their related catabolic genes expression were analyzed. RESULTS: Interleukin-1ß (IL-1ß) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10(-8) M Ecd, the catabolic effects of IL-1ß on articular cartilage were scavenged. CONCLUSION: In conclusions, Ecd can reduce the IL-1ß-induced inflammatory effect of the cartilage. Ecd may suppress IL-1ß-induced cartilage catabolism via HIF-2α pathway.